Brown Stephanie, Meredith Timothy, Swoboda Jonathan, Walker Suzanne
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Chem Biol. 2010 Oct 29;17(10):1101-10. doi: 10.1016/j.chembiol.2010.07.017.
Wall teichoic acids (WTAs) are anionic polymers that play key roles in bacterial cell shape, cell division, envelope integrity, biofilm formation, and pathogenesis. B. subtilis W23 and S. aureus both make polyribitol-phosphate (RboP) WTAs and contain similar sets of biosynthetic genes. We use in vitro reconstitution combined with genetics to show that the pathways for WTA biosynthesis in B. subtilis W23 and S. aureus are different. S. aureus requires a glycerol-phosphate primase called TarF in order to make RboP-WTAs; B. subtilis W23 contains a TarF homolog, but this enzyme makes glycerol-phosphate polymers and is not involved in RboP-WTA synthesis. Instead, B. subtilis TarK functions in place of TarF to prime the WTA intermediate for chain extension by TarL. This work highlights the enzymatic diversity of the poorly characterized family of phosphotransferases involved in WTA biosynthesis in Gram-positive organisms.
壁磷壁酸(WTAs)是一种阴离子聚合物,在细菌细胞形态、细胞分裂、包膜完整性、生物膜形成和致病机制中发挥关键作用。枯草芽孢杆菌W23和金黄色葡萄球菌都能合成聚核糖醇磷酸(RboP)壁磷壁酸,且含有相似的生物合成基因集。我们运用体外重建结合遗传学方法,证明了枯草芽孢杆菌W23和金黄色葡萄球菌中壁磷壁酸生物合成途径不同。金黄色葡萄球菌需要一种名为TarF的甘油磷酸引物酶来合成RboP-壁磷壁酸;枯草芽孢杆菌W23含有TarF的同源物,但这种酶合成甘油磷酸聚合物,不参与RboP-壁磷壁酸的合成。相反,枯草芽孢杆菌的TarK替代TarF发挥作用,为TarL进行链延伸的壁磷壁酸中间体提供引物。这项工作突出了革兰氏阳性菌中参与壁磷壁酸生物合成的磷酸转移酶家族的酶多样性,该家族特性鲜为人知。